Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the e xpression of neurotrophic factors and receptors after spinal cord injury ha s not been studied in detail. We investigated levels of mRNA-encoding neuro trophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in no rmal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the ad ult spinal cord was compared with that in the PNS and the neonate spinal co rd. After mechanical injury of the adult rat spinal cord upregulations of N GF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF a nd p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close t o the lesion, and GFR alpha -1 and truncated TrkB mRNA increased in astrocy tes of degenerating white matter. The relatively limited upregulation of ne urotrophic factors in the spinal cord contrasted with the response of affec ted nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS a nd CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response o f the spinal cord tissue to kainic acid was weak. The relative sparseness o f upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributabl e at least partly to lack of trophic support.